Neurological Manifestations of Uremic Encephalopathy Clinical Presentation

Updated: Sep 17, 2018
  • Author: Gabriel Bucurescu, MD, MS; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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  • Uremic encephalopathy (UE) is a consequence of renal failure (RF).

  • Symptoms begin insidiously and are often noticed not by the patients but by their family members or caregivers.

  • In many cases, impairment of the nervous system provides the first indication of metabolic derangements.

  • Symptoms may progress slowly or rapidly.

  • Changes in sensorium include loss of memory, impaired concentration, depression, delusions, lethargy, irritability, fatigue, insomnia, psychosis, stupor, catatonia, and coma.

  • Patients may complain of slurred speech, pruritus, muscle twitches, or restless legs.



Physical findings are variable and depend on the severity of the encephalopathy. Neurologic findings range from normal to a comatose state. Cases of Wernicke syndrome associated with UE have been described in the literature, and Wernicke syndrome has been observed in patients with UE, dialysis dementia, or dialysis disequilibrium syndrome.

Findings include the following:

  • Myoclonic jerks, twitches, or fasciculations (ie, uremic twitch-convulsive syndrome postulated by Adams et al in 1997)

  • Asterixis

  • Chorea [5]

  • Dysarthria

  • Agitation

  • Tetany

  • Seizures, usually generalized tonic-clonic

  • Confusion, stupor, and other alterations in mental status

  • Coma

  • Sleep disorders

Some patients undergoing long-term dialysis acquire dialysis encephalopathy (or dialysis dementia), which is a subacute, progressive, and often fatal disease. [6] Aluminum toxicity either from aluminum phosphate salts or from aluminum in the dialysate were linked to the pathogenesis of dialysis dementia. Starting in the early and mid 1980s, aluminum was actively removed from the dialysate with a large reduction in the incidence of dialysis dementia.

  • Dialysis encephalopathy is believed to be part of a multisystem disease that includes encephalopathy, osteomalacic bone disease, proximal myopathy, and anemia.

  • Symptoms include dysarthria, apraxia, personality changes, psychosis, myoclonus, seizures and, finally, dementia.

  • In most cases, the condition progresses to death in 6 months.

Dialysis disequilibrium syndrome occurs in patients receiving hemodialysis.

  • Symptoms include headache, nausea, emesis, blurred vision, muscular twitching, disorientation, delirium, hypertension, tremors, and seizures.

  • The condition tends to be self-limited and subsides over several hours.

  • Dialysis disequilibrium syndrome is attributed to a reverse urea effect. Urea is cleared more slowly from the brain than from the blood, an effect that causes an osmotic gradient leading to the net flow of water into the brain and to transient cerebral edema.

Posterior reversible leukoencephalopathy syndrome (PRLS), also called reversible leukoencephalopathy syndrome, can occur at any age and can manifest with seizures (either generalized or focal), visual hallucinations, headaches, mental status impairment, and cortical blindness. It is not limited to uremic encephalopathy, but can also be seen in liver and renal transplant patients, pre-eclampsia, hypertension associated with renal disease, or other immunosuppressed states. The characterisitc MRI finding is diffuse attenuation in the cerebral white matter, and may include the brainstem and cerebellum. The disorder is self-limiting and improves if hypertension is controlled. [7]

Complications of renal transplantation can lead to UE. This occurrence has become more common as more patients are receiving renal transplants.

  • This condition is characterized by edema of the white matter.

  • Patients are at risk for primary brain lymphoma and opportunistic infections because of long-term immunosuppression.

Rejection encephalopathy has been observed in patients undergoing transplantation. They have systemic features of acute graft rejection, more than 80% of whom have symptoms in the first 3 months after transplantation. Overall prognosis is good, with rapid recovery after treatment of the rejection episode. The presumed pathology is cytokine production secondary to the rejection process.

Uremic polyneuropathy is the most common neurologic complication of RF.



The exact cause of UE is unknown.

Accumulation of metabolites and, perhaps, imbalance in excitatory and inhibitory neurotransmitters are possible etiologies.

PTH and abnormal calcium control have also been identified as possible important contributing factors.